ITGB3 Gene (Integrin Subunit Beta 3)
Key regulator of platelet aggregation, cell adhesion, and angiogenesis; mutations cause Glanzmann thrombasthenia and other bleeding disorders.
Gene Information Card
| Symbol | ITGB3 |
|---|---|
| Full Name | Integrin Subunit Beta 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.32 |
| NCBI Gene ID | 3690 ncbi.nlm.nih.gov/gene/3690 |
| Ensembl ID | ENSG00000259207 |
| UniProt ID | P05106 |
| OMIM ID | 173470 |
| HGNC ID | 6156 |
| Aliases | CD61, GP3A, GPIIIa, ITGB3, BDPLT2, BDPLT16, GT |
Description
The ITGB3 gene encodes integrin beta 3, a transmembrane glycoprotein that forms heterodimers with integrin alpha subunits (e.g., alphaIIb and alphaV). The alphaIIb/beta3 complex (GPIIb/IIIa) is essential for platelet aggregation and thrombus formation. AlphaV/beta3 mediates cell adhesion, migration, and angiogenesis. Mutations in ITGB3 cause Glanzmann thrombasthenia (GT), a bleeding disorder characterized by defective platelet aggregation. Variants are also associated with susceptibility to coronary artery disease, stroke, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glanzmann thrombasthenia (GT) | Loss-of-function mutations in ITGB3 impair alphaIIb/beta3 integrin expression or function, preventing platelet aggregation. | ClinVar, OMIM |
| Bleeding disorder, platelet-type 16 (BDPLT16) | Heterozygous gain-of-function mutations in ITGB3 cause constitutive activation of alphaIIb/beta3, leading to thrombocytopenia and bleeding. | OMIM, ClinVar |
| Coronary artery disease (CAD) | Polymorphisms (e.g., rs5918, Leu33Pro) alter integrin function, influencing platelet reactivity and thrombotic risk. | NCBI, ClinVar |
| Cancer (e.g., melanoma, ovarian) | Overexpression of alphaV/beta3 promotes tumor cell adhesion, migration, and angiogenesis. | COSMIC, NCBI |
| Osteoporosis | Variants in ITGB3 affect osteoclast function via alphaV/beta3-mediated bone resorption. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | nTPM: 112.3 | High |
| Blood (platelets) | nTPM: 89.7 | High |
| Lung | nTPM: 12.4 | Medium |
| Kidney | nTPM: 8.1 | Low |
| Liver | nTPM: 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | nTPM: 15.2 | Moderate expression |
| K562 (erythroleukemia) | nTPM: 42.1 | High expression |
| MCF7 (breast cancer) | nTPM: 6.8 | Low expression |
| A549 (lung cancer) | nTPM: 9.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.176T>C (p.Leu59Pro) | Missense | Rare (0.01%) | Loss of function; associated with Glanzmann thrombasthenia |
| c.233C>T (p.Thr78Ile) | Missense | Rare (0.005%) | Loss of function; impaired integrin surface expression |
| c.517T>C (p.Cys173Arg) | Missense | Rare (0.002%) | Loss of function; disrupts disulfide bond, protein misfolding |
| c.1960G>A (p.Val654Met) | Missense | 0.1% (rs5918) | Gain of function; increased platelet aggregation, CAD risk |
| c.2332C>T (p.Arg778Trp) | Missense | Rare (0.003%) | Gain of function; constitutive activation, BDPLT16 |
Mutation functional classification
Loss of Function (LOF)
Most ITGB3 mutations causing Glanzmann thrombasthenia are loss-of-function, leading to reduced or absent integrin beta 3 protein on the platelet surface, defective fibrinogen binding, and impaired platelet aggregation.
Gain of Function (GOF)
Gain-of-function mutations (e.g., p.Val654Met, p.Arg778Trp) result in constitutive activation of the alphaIIb/beta3 integrin, causing spontaneous platelet aggregation, thrombocytopenia, and bleeding tendency (BDPLT16).
Dominant Negative (DN)
Dominant-negative effects are observed in some heterozygous missense mutations that disrupt integrin heterodimer assembly, reducing functional integrin complexes on the cell surface.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Integrin signaling pathway (KEGG: hsa04510)
• Focal adhesion (KEGG: hsa04510)
• Platelet activation (KEGG: hsa04611)
• ECM-receptor interaction (KEGG: hsa04512)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
Integrin beta 3 (CD61) is a 788-amino-acid transmembrane protein that forms heterodimers with integrin alphaIIb (CD41) or alphaV. The alphaIIb/beta3 complex (GPIIb/IIIa) is the major platelet fibrinogen receptor, essential for platelet aggregation and hemostasis. The alphaV/beta3 complex mediates cell adhesion to vitronectin, fibronectin, and other ECM proteins, playing roles in angiogenesis, tumor metastasis, and bone resorption. The protein contains an extracellular domain with a von Willebrand factor type A domain, a transmembrane domain, and a short cytoplasmic tail that interacts with cytoskeletal and signaling proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGB3 Knockout HEK293 Cell Line | EDJ-KQ818 | Human | 3690 | Details Get a Quote |
| ITGB3 Knockout HeLa Cell Line | EDJ-KQ18290 | Human | 3690 | Details Get a Quote |
| ITGB3BP Knockout HEK293 Cell Line | EDJ-KQ51104 | Human | 23421 | Details Get a Quote |
| ITGB3BP Knockout HeLa Cell Line | EDJ-KQ55733 | Human | 23421 | Details Get a Quote |
| ITGB3 Knockout A-549 Cell Line | EDJ-KQ62156 | Human | 3690 | Details Get a Quote |
| ITGB3BP Knockout A-549 Cell Line | EDJ-KQ64232 | Human | 23421 | Details Get a Quote |
| ITGB3 Knockout HCT 116 Cell Line | EDJ-KQ70645 | Human | 3690 | Details Get a Quote |
| ITGB3BP Knockout HCT 116 Cell Line | EDJ-KQ72677 | Human | 23421 | Details Get a Quote |
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